CN115920973A - Preparation method of deuterated methanol - Google Patents
Preparation method of deuterated methanol Download PDFInfo
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- CN115920973A CN115920973A CN202310227599.1A CN202310227599A CN115920973A CN 115920973 A CN115920973 A CN 115920973A CN 202310227599 A CN202310227599 A CN 202310227599A CN 115920973 A CN115920973 A CN 115920973A
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- deuterated methanol
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- methanol
- deuterated
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- OKKJLVBELUTLKV-MZCSYVLQSA-N Deuterated methanol Chemical compound [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-N 0.000 title claims abstract description 110
- 238000002360 preparation method Methods 0.000 title claims abstract description 39
- 239000003054 catalyst Substances 0.000 claims abstract description 60
- 238000006243 chemical reaction Methods 0.000 claims abstract description 33
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 claims abstract description 30
- 239000001569 carbon dioxide Substances 0.000 claims abstract description 15
- 229910002092 carbon dioxide Inorganic materials 0.000 claims abstract description 15
- 239000007789 gas Substances 0.000 claims abstract description 14
- YZCKVEUIGOORGS-OUBTZVSYSA-N Deuterium Chemical compound [2H] YZCKVEUIGOORGS-OUBTZVSYSA-N 0.000 claims abstract description 13
- 229910052805 deuterium Inorganic materials 0.000 claims abstract description 13
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 11
- 239000001257 hydrogen Substances 0.000 claims abstract description 11
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 10
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 6
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 5
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims abstract description 5
- 238000000034 method Methods 0.000 claims description 11
- 239000000126 substance Substances 0.000 claims description 10
- 239000000203 mixture Substances 0.000 claims description 7
- 230000003197 catalytic effect Effects 0.000 abstract description 12
- 238000003786 synthesis reaction Methods 0.000 abstract description 10
- 238000011112 process operation Methods 0.000 abstract description 3
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 abstract 1
- 229910052799 carbon Inorganic materials 0.000 abstract 1
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 90
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 36
- 239000000047 product Substances 0.000 description 24
- 238000003756 stirring Methods 0.000 description 23
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 21
- 238000005481 NMR spectroscopy Methods 0.000 description 17
- 238000001914 filtration Methods 0.000 description 17
- 239000012299 nitrogen atmosphere Substances 0.000 description 16
- 239000000706 filtrate Substances 0.000 description 15
- 239000013067 intermediate product Substances 0.000 description 14
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 12
- 239000002904 solvent Substances 0.000 description 12
- 239000002994 raw material Substances 0.000 description 11
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 10
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 9
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
- 229940079593 drug Drugs 0.000 description 9
- 239000003814 drug Substances 0.000 description 9
- 239000000243 solution Substances 0.000 description 9
- 230000015572 biosynthetic process Effects 0.000 description 7
- 150000001875 compounds Chemical class 0.000 description 7
- XLOMVQKBTHCTTD-UHFFFAOYSA-N Zinc monoxide Chemical compound [Zn]=O XLOMVQKBTHCTTD-UHFFFAOYSA-N 0.000 description 6
- 239000003208 petroleum Substances 0.000 description 6
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 5
- ZQVLPMNLLKGGIU-UHFFFAOYSA-N 5-bromopyridine-2-carbaldehyde Chemical compound BrC1=CC=C(C=O)N=C1 ZQVLPMNLLKGGIU-UHFFFAOYSA-N 0.000 description 5
- 229960000583 acetic acid Drugs 0.000 description 5
- 238000004587 chromatography analysis Methods 0.000 description 5
- 230000000052 comparative effect Effects 0.000 description 5
- 238000001514 detection method Methods 0.000 description 5
- 239000012362 glacial acetic acid Substances 0.000 description 5
- USVQCSLXWUKOGP-UHFFFAOYSA-N 6-bromo-5-methoxypyridine-2-carbaldehyde Chemical compound COC1=CC=C(C=O)N=C1Br USVQCSLXWUKOGP-UHFFFAOYSA-N 0.000 description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
- 238000002156 mixing Methods 0.000 description 4
- 238000006467 substitution reaction Methods 0.000 description 4
- PDJZOFLRRJQYBF-UHFFFAOYSA-N 4-(aminomethyl)-n,n-dimethylaniline Chemical compound CN(C)C1=CC=C(CN)C=C1 PDJZOFLRRJQYBF-UHFFFAOYSA-N 0.000 description 3
- QPLDLSVMHZLSFG-UHFFFAOYSA-N Copper oxide Chemical compound [Cu]=O QPLDLSVMHZLSFG-UHFFFAOYSA-N 0.000 description 3
- 239000005751 Copper oxide Substances 0.000 description 3
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- 238000004440 column chromatography Methods 0.000 description 3
- 229910000431 copper oxide Inorganic materials 0.000 description 3
- 238000004090 dissolution Methods 0.000 description 3
- 238000002386 leaching Methods 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- 239000011259 mixed solution Substances 0.000 description 3
- 230000007935 neutral effect Effects 0.000 description 3
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 3
- 238000011160 research Methods 0.000 description 3
- 238000005406 washing Methods 0.000 description 3
- 239000011787 zinc oxide Substances 0.000 description 3
- SMIXZZMSWYOQPW-UHFFFAOYSA-N (4-nitrophenyl)methylazanium;chloride Chemical compound [Cl-].[NH3+]CC1=CC=C([N+]([O-])=O)C=C1 SMIXZZMSWYOQPW-UHFFFAOYSA-N 0.000 description 2
- SORXTEGDLMCGFT-UHFFFAOYSA-N 4-[amino(phenyl)methyl]phenol Chemical compound C=1C=C(O)C=CC=1C(N)C1=CC=CC=C1 SORXTEGDLMCGFT-UHFFFAOYSA-N 0.000 description 2
- PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 2
- -1 amino compound Chemical class 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 238000004821 distillation Methods 0.000 description 2
- 230000007613 environmental effect Effects 0.000 description 2
- 239000005431 greenhouse gas Substances 0.000 description 2
- 229910052757 nitrogen Inorganic materials 0.000 description 2
- MUMZUERVLWJKNR-UHFFFAOYSA-N oxoplatinum Chemical compound [Pt]=O MUMZUERVLWJKNR-UHFFFAOYSA-N 0.000 description 2
- 229910003446 platinum oxide Inorganic materials 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- 229910052723 transition metal Inorganic materials 0.000 description 2
- 150000003624 transition metals Chemical class 0.000 description 2
- AHOUBRCZNHFOSL-YOEHRIQHSA-N (+)-Casbol Chemical class C1=CC(F)=CC=C1[C@H]1[C@H](COC=2C=C3OCOC3=CC=2)CNCC1 AHOUBRCZNHFOSL-YOEHRIQHSA-N 0.000 description 1
- MKJIEFSOBYUXJB-HOCLYGCPSA-N (3S,11bS)-9,10-dimethoxy-3-isobutyl-1,3,4,6,7,11b-hexahydro-2H-pyrido[2,1-a]isoquinolin-2-one Chemical class C1CN2C[C@H](CC(C)C)C(=O)C[C@H]2C2=C1C=C(OC)C(OC)=C2 MKJIEFSOBYUXJB-HOCLYGCPSA-N 0.000 description 1
- RKUJVUAGFYNDLE-UHFFFAOYSA-N 4-nitrobenzamide;hydrochloride Chemical compound Cl.NC(=O)C1=CC=C([N+]([O-])=O)C=C1 RKUJVUAGFYNDLE-UHFFFAOYSA-N 0.000 description 1
- UGFAIRIUMAVXCW-UHFFFAOYSA-N Carbon monoxide Chemical compound [O+]#[C-] UGFAIRIUMAVXCW-UHFFFAOYSA-N 0.000 description 1
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical group C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 1
- 150000004940 Tofacitinib derivatives Chemical class 0.000 description 1
- KZNMRPQBBZBTSW-UHFFFAOYSA-N [Au]=O Chemical compound [Au]=O KZNMRPQBBZBTSW-UHFFFAOYSA-N 0.000 description 1
- AXRYRYVKAWYZBR-GASGPIRDSA-N atazanavir Chemical class C([C@H](NC(=O)[C@@H](NC(=O)OC)C(C)(C)C)[C@@H](O)CN(CC=1C=CC(=CC=1)C=1N=CC=CC=1)NC(=O)[C@@H](NC(=O)OC)C(C)(C)C)C1=CC=CC=C1 AXRYRYVKAWYZBR-GASGPIRDSA-N 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 229910002091 carbon monoxide Inorganic materials 0.000 description 1
- 238000006555 catalytic reaction Methods 0.000 description 1
- 239000013064 chemical raw material Substances 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 238000007405 data analysis Methods 0.000 description 1
- 230000008034 disappearance Effects 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 238000004817 gas chromatography Methods 0.000 description 1
- 229910001922 gold oxide Inorganic materials 0.000 description 1
- 150000002431 hydrogen Chemical class 0.000 description 1
- 230000000977 initiatory effect Effects 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- TWNQGVIAIRXVLR-UHFFFAOYSA-N oxo(oxoalumanyloxy)alumane Chemical compound O=[Al]O[Al]=O TWNQGVIAIRXVLR-UHFFFAOYSA-N 0.000 description 1
- SJLOMQIUPFZJAN-UHFFFAOYSA-N oxorhodium Chemical compound [Rh]=O SJLOMQIUPFZJAN-UHFFFAOYSA-N 0.000 description 1
- ISWRGOKTTBVCFA-UHFFFAOYSA-N pirfenidone Chemical class C1=C(C)C=CC(=O)N1C1=CC=CC=C1 ISWRGOKTTBVCFA-UHFFFAOYSA-N 0.000 description 1
- 229910003450 rhodium oxide Inorganic materials 0.000 description 1
- 238000007086 side reaction Methods 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- OEKWJQXRCDYSHL-FNOIDJSQSA-N ticagrelor Chemical class C1([C@@H]2C[C@H]2NC=2N=C(N=C3N([C@H]4[C@@H]([C@H](O)[C@@H](OCCO)C4)O)N=NC3=2)SCCC)=CC=C(F)C(F)=C1 OEKWJQXRCDYSHL-FNOIDJSQSA-N 0.000 description 1
- 239000003053 toxin Substances 0.000 description 1
- PNVNVHUZROJLTJ-UHFFFAOYSA-N venlafaxine Chemical class C1=CC(OC)=CC=C1C(CN(C)C)C1(O)CCCCC1 PNVNVHUZROJLTJ-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/52—Improvements relating to the production of bulk chemicals using catalysts, e.g. selective catalysts
Landscapes
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention discloses a preparation method of fully deuterated methanol, which relates to the technical field of organic synthesis and comprises the following steps: a catalyst having a structure represented by formula (1) or formula (2):
(1) Or
(2) Wherein R is 1 Independently selected from hydrogen or phenyl; r 2 Independently selected from hydroxy or nitro or-N (CH) 3 ) 2 Catalyzing the reaction of deuterium gas and carbon dioxideThe deuterated methanol is prepared. The preparation method provided by the invention is simple in process operation, the catalyst with a designed novel structure has higher catalytic activity, and the fully deuterated methanol obtained by catalyzing the carbon dioxide deuteration reaction has higher product purity and product yield and high application value.
Description
Technical Field
The invention belongs to the technical field of organic synthesis, and particularly relates to a preparation method of deuterated methanol.
Background
Deuterium is a stable form of nonradioactive isotope of hydrogen in nature, and has larger atomic mass than hydrogen, so that a C-D bond is more stable than a C-H bond, and the deuterium is widely applied to biological medicines, photoelectric display and nuclear magnetic resonance detection. For example, substitution of deuterium for hydrogen in a drug molecule can block metabolic sites and reduce the production of toxic metabolites. The deuterated methanol is an important chemical raw material and a deuterated drug intermediate. The fully deuterated methanol has a structure shown in the specification: CD (compact disc) 3 OD is used. The reagent is a common nuclear magnetic resonance hydrogen spectrum detection reagent in chemical synthesis, and is widely applied to experimental research work. In recent years, as deuterated drugs become a hot spot for drug research, deuterated methanol is widely applied to research of deuterated drugs. Currently, many deuterated drugs are clinically researched, such as deuterated tetrabenazine, deuterated venlafaxine, deuterated tofacitinib, deuterated ticagrelor, deuterated pirfenidone, deuterated paroxetine, deuterated atazanavir and other deuterated drugs.
At present, methods for preparing deuterated methanol are also reported in the prior art, for example, chinese patents CN112321388A, CN112675875A, CN11116313A, CN108250041A and CN109078638A all disclose methods for preparing deuterated methanol by using deuterium gas and carbon monoxide gas as raw materials, wherein, the catalyst used in chinese patent CN11116313A is at least one of zinc oxide, copper oxide, aluminum oxide and platinum oxide, and the catalyst used in chinese patent CN108250041A is one or a combination of gold oxide, platinum oxide and rhodium oxide; chinese patent CN109078638A discloses CuZnCeAlO as a catalyst, and chinese patent CN112675875A also discloses CuZnAlO as a catalyst.
However, the preparation method of common methanol is not suitable for the preparation of fully deuterated methanol, and the currently disclosed technical data has the problems of harsh reaction conditions, complex process, low total yield and the like, and the synthetic technology for industrially producing deuterated methanol is not available, so that the step of commercially developing deuterated drugs is limited.
Disclosure of Invention
The invention aims to provide a preparation method of the deuterated methanol, which is simple in process operation, adopts a designed catalyst with a novel structure, has higher catalytic activity, and has higher product purity and product yield and high application value when catalyzing the deuterated methanol obtained by the carbon dioxide deuteration reaction.
The technical scheme adopted by the invention for realizing the purpose is as follows:
a catalyst for preparing deuterated methanol has a chemical structural formula as shown in the specification:
Wherein R is 1 Independently selected from hydrogen or phenyl; r 2 Independently selected from hydroxy or nitro or-N (CH) 3 ) 2 。
The invention designs and synthesizes a series of transition metal complexes containing N, N bidentate ligands, the transition metal complexes can effectively catalyze carbon dioxide deuteration reaction to generate deuterium-substituted methanol as a catalyst, and by adjusting and changing substituent groups and substitution positions on benzene rings or pyridine rings in the structure, the initiation rate and catalytic activity of the catalyst can be effectively improved by improving electronic effect or changing the size of surrounding steric hindrance, the deuterium-substituted methanol is prepared by catalyzing carbon dioxide and deuterium gas, and the purity and yield of the product are obviously increased. The catalyst designed and prepared by the invention can effectively catalyze carbon dioxide and deuterium gas to prepare high-quality deuterated methanol, provides a new idea for a process route for preparing deuterated methanol from carbon dioxide, and has high application value.
Preferably, R 1 Selected from hydrogen; r 2 Is selected from-N (CH) 3 ) 2 。
Preferably, R 1 Selected from hydrogen; r 2 Is selected from nitro.
Preferably, R 1 Is selected from phenyl; r is 2 Selected from hydroxyl groups.
Specifically, the catalyst for preparing the deuterated methanol is at least one selected from the following structures:
the invention also discloses a preparation method of the structure shown in the formula (1), which comprises the following steps:
adding 5-bromo-2-pyridinecarboxaldehyde and amino compounds into anhydrous oxygen-free methanol under nitrogen atmosphere, stirring at room temperature until reaction raw materials disappear, and adding NaBH 4 Continuously stirring at room temperature until the intermediate product disappears, stopping the reaction, and separating and purifying to obtain an intermediate;
taking the intermediate, [ Cp IrCl ] in nitrogen atmosphere 2 ] 2 Adding absolute methanol, stirring at room temperature for reaction, and separating and purifying.
Preferably, the molar ratio of the 5-bromo-2-pyridinecarboxaldehyde to the amino compound is 1 to 1.4.
Preferably, naBH 4 The molar ratio of the compound to 5-bromo-2-pyridinecarboxaldehyde is 3.5 to 4.5.
Preferably, the intermediate is reacted with [ CpIrCl [ ] 2 ] 2 The molar ratio of (1).
The invention also discloses a preparation method of the structure shown in the formula (2), which comprises the following steps:
under the nitrogen atmosphere, 6-bromine-5-methoxypyridinal and amino compounds are added into anhydrous oxygen-free methanol, stirred at room temperature until reaction raw materials disappear, and added with NaBH 4 Continuously stirring at room temperature until the intermediate product disappears, stopping reaction, and separating and purifying to obtain an intermediate product 1;
mixing the intermediate product 1, hydrobromic acid and glacial acetic acid, stirring and reacting at 80-90 ℃ for 2-3 h, and then separating and purifying to obtain an intermediate product 2;
taking intermediate product 2 [ (C) under nitrogen atmosphere 6 H 6 )RuCl 2 ] 2 Adding absolute ethyl alcohol, stirring and reacting for 10 to 12h at 70 to 75 ℃ in the dark, and then separating and purifying.
Preferably, the molar ratio of the 6-bromo-5-methoxypyridinal to the amino compound is 1.
Preferably, naBH 4 The molar ratio of the compound to 6-bromo-5-methoxypyridinal is 3.5 to 4.5.
Preferably, the dosage ratio of the intermediate product 1 to the hydrobromic acid is 0.08 to 0.1mmol; the dosage ratio of the intermediate product 1 to the glacial acetic acid is 0.15-0.25mmol.
Preferably, intermediate 2, [ (C) 6 H 6 )RuCl 2 ] 2 The molar ratio of (A) to (B) is 1.8 to 2.2.
Preferably, the amino-based compound is selected from 4-dimethylaminobenzylamine, 4-nitrobenzylamine hydrochloride or 4- (aminophenylmethyl) phenol.
The invention also discloses a preparation method of the fully deuterated methanol, which comprises the following steps: the catalyst is adopted to catalyze the reaction of deuterium gas and carbon dioxide to prepare the fully deuterated methanol. The catalyst with the novel structure is applied to the preparation process of the deuterium-substituted methanol, the carbon dioxide is used as a raw material to catalyze the catalyst to react with deuterium gas to prepare the deuterium-substituted methanol, better catalytic performance is shown, and the purity and the yield of the prepared deuterium-substituted methanol are obviously improved. The method provided by the invention has the characteristics of high selectivity, good conversion rate, high purity and less side reaction, the product yield reaches more than 80%, and the purity of the prepared deuterium-substituted methanol can reach more than 99.0% through simple rectification; the preparation process is simple, is suitable for refined production and popularization, and has good application value. In addition, the catalyst designed and prepared by the invention is used in a compound way, and is applied to catalytic combination in a compound coordination wayThe fully deuterated methanol has higher catalytic activity, the product quality is obviously improved, and the purity and the yield are both obviously increased. Meanwhile, the invention prepares and obtains chemicals with high added value by taking carbon dioxide as raw material to relieve or improve greenhouse gas CO 2 The energy crisis and the environmental problem caused by the method provide a new idea.
Preferably, the volume ratio of the deuterium gas to the carbon dioxide is 1.
Preferably, the reaction pressure is 4 to 6MP; the reaction temperature is 200 to 300 ℃.
More preferably, the catalyst comprises a mixture of structures represented by formula (1) and formula (2).
Preferably, the mass ratio of the structure represented by the formula (1) to the structure represented by the formula (2) is 1 to 1.
The invention also discloses the application of the catalyst with the structure shown in the formula (1) or the formula (2) in the preparation of the deuterium-substituted methanol.
Compared with the prior art, the invention has the following beneficial effects:
the catalyst with the novel structure is applied to the preparation process of the deuterium-substituted methanol, the deuterium-substituted methanol is prepared by catalyzing the reaction of carbon dioxide and deuterium gas, excellent catalytic performance is shown, and compared with the prior art, the purity and yield of the deuterium-substituted methanol prepared by the method are obviously improved. In addition, the catalyst designed and prepared by the invention is used in a compound way, is compounded and cooperated, is applied to the catalysis and synthesis of the fully deuterated methanol, shows higher catalytic activity, and obviously increases the purity and yield of the product. The invention prepares and obtains chemicals with high added value by taking carbon dioxide as a raw material, and aims to relieve or improve greenhouse gas CO 2 The energy crisis and the environmental problem caused by the method provide a new idea.
Therefore, the preparation method of the deuterated methanol is simple in process operation, the catalyst with the designed novel structure is adopted, the catalytic activity is higher, the deuterated methanol obtained by catalyzing the carbon dioxide deuteration reaction has higher product purity and product yield, and the application value is high.
Detailed Description
In order to make the objects, technical solutions and advantages of the embodiments of the present invention clearer, the following describes each embodiment of the present invention in detail with reference to the embodiments. However, it will be appreciated by those of ordinary skill in the art that numerous technical details are set forth in order to provide a better understanding of the present application in various embodiments of the present invention. However, the technical solution claimed in the present application can be implemented without these technical details and various changes and modifications based on the following embodiments.
Example 1:
the chemical structure of catalyst I is as follows:
preparation of the catalyst I for the synthesis of deuterated methanol:
under the nitrogen atmosphere, 0.3mmol of 5-bromo-2-pyridinecarboxaldehyde and 0.3mmol of 4-dimethylaminobenzylamine are added into 10mL of anhydrous oxygen-free methanol, the mixture is stirred at room temperature, after TCL detection shows that the reaction raw material disappears, 1.2mmol of NaBH is added 4 Stirring at room temperature, detecting with TCL to show that the intermediate product disappears, stopping reaction, distilling under reduced pressure to remove solvent, adding CH 2 Cl 2 Filtering and collecting filtrate, and separating and purifying by reduced pressure distillation and plate chromatography (a developing solvent is petroleum ether: ethyl acetate = 5; 1 H NMR（400 MHz，CDCl 3 ）：δ：8.47、7.93、7.79（3H，Py-H），7.08、6.75（4H，Ar-H），4.10、3.68（4H，-CH 2 ），2.99（6H，-CH 3 ）；
taking 0.175mmol of product A, 0.086mmol of [ Cp ] IrCl and under the nitrogen atmosphere 2 ] 2 Adding 20mL of anhydrous methanol, stirring at room temperature for 16h, then filtering and collecting filtrate, distilling under reduced pressure, washing by adopting a mixed solution of n-hexane/diethyl ether (v/v, 1; 1 H NMR（400 MHz，CDCl 3 ）：δ：8.04、7.53、7.01（3H，Py-H），7.20~7.45（4H，Ar-H），4.28、4.11（4H，-CH 2 ），3.09（6H，-CH 3 ），1.94（15H，-CH 3 ）。
example 2:
the chemical structure of catalyst J is as follows:
preparation of the catalyst J for the synthesis of deuterated methanol:
adding 0.3mmol of 5-bromo-2-pyridinecarboxaldehyde and 0.3mmol of 4-nitrobenzamide hydrochloride into 10mL of anhydrous oxygen-free methanol under nitrogen atmosphere, stirring at room temperature, detecting with TCL to show that the reaction raw material disappears, and adding 1.2mmol of NaBH 4 Stirring at room temperature, detecting with TCL to show that the intermediate product disappears, stopping reaction, distilling under reduced pressure to remove solvent, adding CH 2 Cl 2 Filtering, collecting filtrate, distilling under reduced pressure, and separating and purifying by plate chromatography (the developing solvent is petroleum ether: ethyl acetate =5:1,v/v) to obtain a product B; 1 H NMR（400 MHz，CDCl 3 ）：δ：8.55、7.91、7.80（3H，Py-H），8.31、7.90（4H，Ar-H），4.15、3.75（4H，-CH 2 ）；
taking 0.175mmol of product B and 0.086mmol of Cp IrCl under the nitrogen atmosphere 2 ] 2 Adding 20mL of anhydrous methanol, stirring at room temperature for 16h, then filtering and collecting filtrate, distilling under reduced pressure, washing by adopting a mixed solution of n-hexane/diethyl ether (v/v, 1; 1 H NMR（400 MHz，CDCl 3 ）：δ：8.10、7.61、6.94（3H，Py-H），7.25~7.48（4H，Ar-H），4.20、4.07（4H，-CH 2 ），1.89（15H，-CH 3 ）。
example 3:
the chemical structure of catalyst K is as follows:
preparation of the catalyst K for the synthesis of deuterated methanol:
under nitrogen atmosphere, 0.3mmol of 5 is takenAdding-bromo-2-pyridinecarboxaldehyde and 0.3mmol4- (aminophenylmethyl) phenol into 10mL anhydrous oxygen-free methanol, stirring at room temperature, detecting with TCL to show that the reaction raw material disappears, adding 1.2mmol NaBH 4 Stirring at room temperature, detecting with TCL to show that the intermediate product disappears, stopping reaction, distilling under reduced pressure to remove solvent, adding CH 2 Cl 2 Filtering, collecting filtrate, distilling under reduced pressure, and separating and purifying by plate chromatography (the developing solvent is petroleum ether: ethyl acetate =5:1,v/v) to obtain a product C; 1 H NMR（400 MHz，CDCl 3 ）：δ：8.54、7.88、7.81（3H，Py-H），7.20~7.45（5H，Ar-H），7.06、6.62（4H，Ar-H），5.21（1H，-CH），4.10（2H，-CH 2 ）；
taking 0.175mmol of product C and 0.086mmol of Cp IrCl under the nitrogen atmosphere 2 ] 2 Adding 20mL of anhydrous methanol, stirring at room temperature for 16h, then filtering and collecting filtrate, distilling under reduced pressure, washing with a mixed solution of n-hexane/diethyl ether (v/v, 1); 1 H NMR（400 MHz，CDCl 3 ）：δ：8.54、7.73、7.69（3H，Py-H），7.35~7.60（5H，Ar-H），7.40、7.09（4H，Ar-H），6.18（1H，-CH），4.18（2H，-CH 2 ），2.11（15H，-CH 3 ）。
example 4:
the chemical structure of catalyst O is as follows:
preparation of the catalyst O for the synthesis of deuterated methanol:
under the nitrogen atmosphere, 0.3mmol of 6-bromo-5-methoxypyridinal and 0.3mmol of 4-dimethylaminobenzylamine are added into 10mL of anhydrous oxygen-free methanol, stirred at room temperature, and after TCL detection shows that the reaction raw materials disappear, 1.2mmol of NaBH is added 4 Stirring at room temperature, detecting with TCL to show that the intermediate product disappears, stopping reaction, distilling under reduced pressure to remove solvent, adding CH 2 Cl 2 And the filtrate is filtered and collected, distilled under reduced pressure, and chromatographed on a plate (the developing solvent is petroleum ether: ethyl acetate =5v) separating and purifying to obtain a product M; 1 H NMR（400 MHz，CDCl 3 ）：δ：7.83、7.51（2H，Py-H），7.11、6.68（4H，Ar-H），4.16、3.62（4H，-CH 2 ），3.85、2.99（9H，-CH 3 ）；
mixing 0.18mmol of product M, 2mL of hydrobromic acid and 10mL of glacial acetic acid, stirring at 85 ℃, absorbing tail gas by using a sodium hydroxide solution, and reacting for 2h; then adding 1M KOH solution to adjust the reaction system to be neutral, distilling under reduced pressure, adding CH 2 Cl 2 Extracting with methanol, filtering, collecting filtrate, adding anhydrous sodium sulfate, filtering, collecting filtrate, distilling under reduced pressure, and performing column chromatography (developing agent is CH) 2 Cl 2 : methanol = 10) to give product M1; 1 H NMR（400 MHz，CDCl 3 ）：δ：7.80、7.55（2H，Py-H），7.08、6.72（4H，Ar-H），4.15、3.64（4H，-CH 2 ），3.00（6H，-CH 3 ）；
under nitrogen atmosphere, 0.120mmol of product M1 and 0.06mmol of [ (C) 6 H 6 )RuCl 2 ] 2 Adding 10mL of absolute ethyl alcohol, stirring for 10h at 70 ℃ in the dark condition, then distilling under reduced pressure, adding 8mL of dichloromethane for dissolution, then adding 15mL of ethyl acetate, filtering, and leaching with ethyl acetate and n-hexane to obtain a catalyst O; 1 H NMR（400 MHz，CDCl 3 ）：δ：8.89、8.24（2H，Py-H），7.74、7.43（4H，Ar-H），6.07（6H，-CH），4.54、3.98（4H，-CH 2 ），3.11（6H，-CH 3 ）。
example 5:
the chemical structure of catalyst P is as follows:
preparation of the catalyst P for the synthesis of deuterated methanol:
under the nitrogen atmosphere, 0.3mmol of 6-bromo-5-methoxypyridinal and 0.3mmol of 4-nitrobenzyl amine hydrochloride are added into 10mL of anhydrous oxygen-free methanol, stirred at room temperature, and after TCL detection shows that the reaction raw material disappears, 1.2mmol of NaBH is added 4 Stirring at room temperature, detecting with TCL to show that the intermediate product disappears, stopping reaction, distilling under reduced pressure to remove solvent, adding CH 2 Cl 2 Filtering and collecting filtrate, and separating and purifying by reduced pressure distillation and plate chromatography (a developing solvent is petroleum ether: ethyl acetate = 5); 1 H NMR（400 MHz，CDCl 3 ）：δ：7.76、7.49（2H，Py-H），8.26、7.98（4H，Ar-H），4.11、3.71（4H，-CH 2 ），3.87（3H，-CH 3 ）；
mixing 0.18mmol of product N, 2mL of hydrobromic acid and 10mL of glacial acetic acid, stirring at 85 ℃, absorbing tail gas by using a sodium hydroxide solution, and reacting for 2 hours; then adding 1M KOH solution to adjust the reaction system to be neutral, distilling under reduced pressure, adding CH 2 Cl 2 Extracting with methanol, filtering, collecting filtrate, adding anhydrous sodium sulfate, filtering, collecting filtrate, distilling under reduced pressure, and performing column chromatography (developing agent is CH) 2 Cl 2 : methanol = 10) to give product N1; 1 H NMR（400 MHz，CDCl 3 ）：δ：7.78、7.53（2H，Py-H），8.31、7.93（4H，Ar-H），4.14、3.76（4H，-CH 2 ）；
under nitrogen atmosphere, 0.120mmol of product N1 and 0.06mmol of [ (C) 6 H 6 )RuCl 2 ] 2 Adding 10mL of absolute ethyl alcohol, stirring for 10h at 70 ℃ in the dark condition, then distilling under reduced pressure, adding 8mL of dichloromethane for dissolution, then adding 15mL of ethyl acetate, filtering, and leaching with ethyl acetate and n-hexane to obtain a catalyst P; 1 H NMR（400 MHz，CDCl 3 ）：δ：8.75、8.36（2H，Py-H），8.69、8.23（4H，Ar-H），5.89（6H，-CH），4.63、4.15（4H，-CH 2 ）。
example 6:
the chemical structure of catalyst Q is as follows:
preparation of the catalyst Q for synthesis of deuterated methanol:
under nitrogen atmosphere, 0.3mmol of 6-bromo-5-methyl is takenOxopyridinal and 0.3mmol of 4- (aminophenylmethyl) phenol were added to 10mL of anhydrous, oxygen-free methanol, stirred at room temperature, and after disappearance of the starting material as detected by TCL, 1.2mmol of NaBH was added 4 Stirring at room temperature, detecting with TCL to show that the intermediate product disappears, stopping reaction, distilling under reduced pressure to remove solvent, adding CH 2 Cl 2 Filtering, collecting filtrate, distilling under reduced pressure, and separating and purifying by plate chromatography (the developing solvent is petroleum ether: ethyl acetate =5:1,v/v) to obtain a product L; 1 H NMR（400 MHz，CDCl 3 ）：δ：7.85、7.60（2H，Py-H），7.18~7.42（5H，Ar-H），7.02、6.59（4H，Ar-H），5.16（1H，-CH），4.18（2H，-CH 2 ），3.80（3H，-CH 3 ）；
mixing 0.18mmol of product L, 2mL of hydrobromic acid and 10mL of glacial acetic acid, stirring at 85 ℃, absorbing tail gas by using a sodium hydroxide solution, and reacting for 2 hours; then adding 1M KOH solution to adjust the reaction system to be neutral, distilling under reduced pressure, adding CH 2 Cl 2 Extracting with methanol, filtering, collecting filtrate, adding anhydrous sodium sulfate, filtering, collecting filtrate, distilling under reduced pressure, and performing column chromatography (developing agent is CH) 2 Cl 2 : methanol = 10) to give product L1; 1 H NMR（400 MHz，CDCl 3 ）：δ：7.83、7.58（2H，Py-H），7.15~7.40（5H，Ar-H），7.07、6.70（4H，Ar-H），5.23（1H，-CH），4.14（2H，-CH 2 ）；
under nitrogen atmosphere, 0.120mmol of product L1 and 0.06mmol of [ (C) 6 H 6 )RuCl 2 ] 2 Adding 10mL of absolute ethyl alcohol, stirring for 10h at 70 ℃ in the dark condition, then distilling under reduced pressure, adding 8mL of dichloromethane for dissolution, then adding 15mL of ethyl acetate, filtering, and leaching with ethyl acetate and n-hexane to obtain a catalyst Q; 1 H NMR（400 MHz，CDCl 3 ）：δ：8.94、8.53（2H，Py-H），7.45~7.70（5H，Ar-H），7.39、7.01（4H，Ar-H），6.09（6H，-CH），5.53（1H，-CH），4.57（2H，-CH 2 ）。
example 7:
the preparation method of the deuterium-substituted methanol comprises the following steps:
firstly, opening valves of deuterium gas and carbon dioxide, controlling the volume ratio to be 1, premixing, passing through a catalyst bed layer at 240 ℃ (the catalyst prepared in example 1) at the speed of 2L/s under the pressure of 5.2MPa, continuously and circularly reacting for 36h, obtaining a fully deuterated methanol reaction solution in a reaction kettle, and then rectifying to prepare the fully deuterated methanol.
Example 8:
the preparation method of the deuterated methanol is different from that of the example 7 in that: the catalyst was prepared as in example 2.
Example 9:
the preparation method of the deuterated methanol is different from that of the example 7 in that: the catalyst was prepared as in example 3.
Example 10:
the preparation method of the deuterated methanol is different from that of the example 7 in that: the catalyst was prepared as in example 4.
Example 11:
the preparation method of the deuterated methanol is different from that of the example 7 in that: the catalyst was prepared as in example 5.
Example 12:
the preparation method of the deuterated methanol is different from that of the example 7 in that: the catalyst was prepared as in example 6.
Example 13:
the preparation method of the deuterated methanol is different from that of the example 7 in that: the catalyst used was a mixture of the catalysts prepared in example 1 and example 5, in a mass ratio of 1.
Example 14:
the preparation method of the deuterated methanol is different from that of the example 7 in that: the catalyst used was a mixture of the catalysts prepared in example 2 and example 6, in a mass ratio of 1.
Example 15:
the preparation method of the deuterated methanol is different from that of the example 7 in that: the catalyst used was a mixture of the catalysts prepared in example 3 and example 4, in a mass ratio of 1.
Comparative example 1:
the preparation method of the deuterated methanol is different from that of the example 7 in that: the catalyst adopts a mixture of zinc oxide, copper oxide and alumina, and the mass ratio of the zinc oxide to the copper oxide to the alumina is 1.
Test example 1:
the deuterated methanol prepared in examples 7 to 15 and comparative example 1 was tested for purity (as determined by gas chromatography) and yield, and the results are shown in table 1:
TABLE 1 purity and yield test results
| Sample (I) | Purity (%) | Yield (%) |
| Example 7 | 99.5 | 34.8 |
| Example 8 | 99.4 | 38.9 |
| Example 9 | 99.3 | 32.7 |
| Example 10 | 99.4 | 48.3 |
| Example 11 | 99.5 | 56.4 |
| Example 12 | 99.5 | 51.6 |
| Example 13 | 99.9 | 81.5 |
| Example 14 | 99.9 | 86.9 |
| Example 15 | 99.9 | 85.2 |
| Comparative example 1 | 99.1 | 28.6 |
As can be seen from the data analysis in table 1, when the catalysts prepared in examples 1 to 6 of the present invention are applied to a process for preparing deuterated methanol, good catalytic activity is exhibited, and the purity and yield of the deuterated methanol obtained by the preparation are significantly better than those of comparative example 1, which indicates that the catalyst structures designed and prepared in examples 1 to 6 of the present invention have better catalytic activity and can better catalyze the preparation of deuterated methanol. And the purity and yield of the deuterated methanol prepared in examples 13-15 are obviously better than those of examples 7-12 and comparative example 1, which shows that the catalyst structures designed and prepared in examples 1-6 of the invention are used in a compound way, and show more excellent catalytic activity when applied to the preparation process of the deuterated methanol.
Conventional techniques in the above embodiments are known to those skilled in the art, and therefore, will not be described in detail herein.
The above description is only for the specific embodiments of the present invention, but the scope of the present invention is not limited thereto, and any person skilled in the art can easily conceive of the changes or substitutions within the technical scope of the present invention, and all the changes or substitutions should be covered within the scope of the present invention. Therefore, the protection scope of the present invention shall be subject to the protection scope of the claims.
Claims (8)
1. A catalyst for preparing deuterated methanol has a chemical structural formula as shown in the specification:
Wherein R is 1 Independently selected from hydrogen or phenyl; r 2 Independently selected from hydroxy or nitro or-N (CH) 3 ) 2 。
2. The catalyst for the preparation of deuterated methanol according to claim 1, wherein R is selected from the group consisting of 1 Selected from hydrogen; r 2 Is selected from-N (CH) 3 ) 2 。
3. The catalyst for preparation of deuterated methanol as recited in claim 1, wherein said R is selected from the group consisting of 1 Selected from hydrogen; r is 2 Is selected from nitro.
4. The catalyst for the preparation of deuterated methanol according to claim 1, wherein R is selected from the group consisting of 1 Is selected from phenyl; r 2 Selected from hydroxyl groups.
5. A method for preparing a deuterated methanol comprises the following steps: the catalyst of claim 1 is used for catalyzing the reaction of deuterium gas and carbon dioxide to prepare the deuterated methanol.
6. The method of claim 5, wherein the catalyst comprises a mixture of structures represented by formula (1) and formula (2).
7. The method of claim 6, wherein the mass ratio of the structure represented by formula (1) to the structure represented by formula (2) is 1 to 2.
8. Use of the catalyst of claim 1 in the preparation of a deuterated methanol.
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